The pharmacokinetics of misonidazole have been studied in 6 patients with special emphasis on determination of the peak concentration in plasma and saliva. Frequent sampling was performed over 4 h and a marked variation in absorption half-life (range 4 - 125 min) and time to peak range (0.5 - 6.5 h) was found. The optimal timing of irradiation is discussed. In addition to a conventional dose, one of the patients received high dose misonidazole; the pharmacokinetics are compared.
Get full access to this article
View all access options for this article.
References
1.
Ash, D.V. , Smith, M.R. & Bugden, R.D. (1979). Distribution of misonidazole in human tumours and normal tissue. Br. J. Cancer, 39, 503-509.
2.
Dische, S. , SAUNDERS, M. I., LEE, M. E., ADAMS, G. E. & FLOCKHART, I. R. (1977 ). Clinical testing of radiosensitiser Ro-07-0582: experience with multiple doses. Br. J. Cancer, 35, 567-579.
3.
Johnston, A. & Woollard, R.C. (1983). STRIPE: An interactive computer program for the analysis of drug pharmacokinetics. J. Pharmacol. Meth. In press.
4.
Notter, G. , Rylander, U. & Turesson, I. (1980). Plasma concentration of misonidazole. Strahlentherapie, 156, 714-718.
5.
Strong, J.M. , Schwade, J.G., Gangji, D., Shoemaker, D.D. & Upton, D.K. (1981). Misonidazole dose and tumour levels. Cancer Clin . Trials, 4, 41-46.
6.
Wiltshire, C.R. , Workman, P., Watson, I.V. & Bleehen, N.M. (1978). Clinical studies with misonidazole. Br. J. Cancer, 37, Suppl. III, 286-289.
7.
Workman, P. , Wiltshire, C.R., Plowman, P.N. & Bleehen, N.M. (1978). Monitoring salivary misonidazole in man: a possible alternative to plasma monitoring. Br. J. Cancer, 38, 709-718.
8.
Workman, P. (1980a). The neurotoxicity of misonidazole: potential modifying role of dexametasone. Br. J. Radiol., 53, 736.
9.
Workman, P. (1980b). Pharmacokinetics of hypoxic cell radiosensitisers: a review. Cancer Clin. Trials, 3, 237-251.
10.
Workman, P. , Bleehen, N.M. & Wiltshire, C.R. (1980). Phenytoin shortens the half-life of hypoxic cell radiosensitizer misonidazole in man: implications for possible reduced toxicity. Br.J. Cancer, 41, 302-304.